rs111464924

Variant names:

• chrX-50042407-C-G
• rs111464924
• NM_001127898.4:c.108C>G

Your query was ambiguous. Multiple possible variants found:

• chrX-50042407-C-G
• chrX-50042407-C-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001127898.4(CLCN5):​c.108C>G​(p.Thr36Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T36T) has been classified as Benign.

• Frequency: Genomes: not found (cov: 23)
• Consequence: CLCN5 NM_001127898.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.294
• Publications: 2 publications found

Genes affected

CLCN5 (HGNC:2023): (chloride voltage-gated channel 5) This gene encodes a member of the ClC family of chloride ion channels and ion transporters. The encoded protein is primarily localized to endosomal membranes and may function to facilitate albumin uptake by the renal proximal tubule. Mutations in this gene have been found in Dent disease and renal tubular disorders complicated by nephrolithiasis. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2013]

CLCN5 Gene-Disease associations (from GenCC):

• Dent disease type 1

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP7: Synonymous conserved (PhyloP=0.294 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001127898.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLCN5	NM_001127898.4	MANE Select	c.108C>G	p.Thr36Thr	synonymous	Exon 4 of 15	NP_001121370.1	P51795-2
	CLCN5	NM_001440756.1		c.108C>G	p.Thr36Thr	synonymous	Exon 4 of 15	NP_001427685.1
	CLCN5	NM_001440757.1		c.108C>G	p.Thr36Thr	synonymous	Exon 4 of 15	NP_001427686.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLCN5	ENST00000376091.8	TSL:2 MANE Select	c.108C>G	p.Thr36Thr	synonymous	Exon 4 of 15	ENSP00000365259.3	P51795-2
	CLCN5	ENST00000376088.7	TSL:2	c.108C>G	p.Thr36Thr	synonymous	Exon 4 of 15	ENSP00000365256.3	P51795-2
	CLCN5	ENST00000854414.1		c.108C>G	p.Thr36Thr	synonymous	Exon 4 of 13	ENSP00000524473.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 25

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	2.5
DANN	Benign	0.45
PhyloP100		0.29

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs111464924; hg19: chrX-49807016;